Cross-linkage of membrane immunoglobulin (Ig) on resting B lymphocytes leads to cellular activation. Biochemical correlates of this cellular activation that have been identified are rapid accumulation of inositol-1,4,5 trisphosphate, rapid increase in cytosolic free calcium concentration (Ca2+)i and striking enhancement in protein kinase C (PKC)-mediated protein phosphorylation. These early biochemical events appear to be important in B cell activation because mimicking them with pharmacologic agents causes B cell activation. We have recently demonstrated that phorbol myristate acetate treatment of B cells blocks signalling normally generated by receptor cross-linkage. Such cells fail to show increased inositol phospholipid metabolism or to elevate (Ca2+)i, indicating that their receptors have been desensitized. These cells are not activated as a result of receptor-cross linkage, providing further support for the importance of these biochemical events in cellular activation. Studies of the substrates of PKC revealed that one of the principal proteins phosphorylated by PMA-treatment of resting B cells was the nuclear intermediate filament protein lamin B. The rapid phosphorylation of a nuclear protein by PMA and by receptor cross-linkage suggests a mechanism through which receptor mediated signals may be communicated to the nucleus. The structural basis of signalling is being studied through the creation of chimeric genes involving exons of class I major histocompatibility complex genes and of Ig genes. These genes have been transferred into B lymphomas and have been shown to be expressed under the influence of interferon. Studies of the capacity of these chimeric membrane proteins to signal upon cross-linkage are now in progress.